Bisphosphonates are currently used as bone-specific palliative treatments for metastatic bone disease in multiple myeloma and breast cancer patients. However, bisphosphonate use has no proven impact on primary tumor burden and overall survival and only moderately reduces skeletal complications. Bisphosphonate conjugates were synthesized using proprietary technology that employs a unique chemical bridge between anti-cancer (nucleotide analogs) or vitamin B6 moieties and a bisphosphonate backbone. The nucleotide-bisphosphonate conjugates were designed to deliver anti-cancer agents specifically to bone. The vitamin B6 conjugates were designed to increase the cellular uptake of bisphosphonates. Preliminary in vitro studies found increased anti-tumor efficacy of select conjugates compared with that of the anti-cancer or bisphosphonate compounds alone. The overall aim of this project is to further develop bisphosphonate conjugate technology and to evaluate the efficacy of these compounds for treatments of metastatic bone disease and secondarily for the treatment of primary tumor and visceral metastases. Select conjugates will be administered to mice inoculated with mammary tumor cells that produce primary breast tumors as well as bone and visceral metastases. Successful development of this new drug-design concept would provide a biologically and commercially superior approach for the treatment and prevention of breast cancer metastases to bone and other organs. Proposed Commercial Application: Not Available.